BACKGROUND: Empiric steroid therapy is the first-line therapy for pediatric nephrotic syndrome, but treatment response is variable. There are few predictors of steroid-responsiveness, although evidence for genetic factors does exist. Single nucleotide polymorphisms (SNPs) have been recently identified in the promoter region of glucocorticoid-induced transcript 1 gene (GLCCI1) which affect steroid-responsiveness in asthmatic patients. Independently, GLCCI1 was identified as a podocyte protein, the loss of which disrupts the function of the glomerular filtration barrier. We therefore examined whether SNPs associated with the steroid-responsive expression of GLCCI1 might predict steroid-responsiveness in nephrotic syndrome. CASE-DIAGNOSIS/TREATMENT: A cohort of 211 pediatric patients with nephrotic syndrome and 102 controls were genotyped; among the cases, 117 were initial steroid responders, while 94 did not respond to oral steroids. No statistically significant differences were noted among the groups, although there was a trend based on the comparison of the small subgroups of steroid-responsive and non-responsive patients with biopsy-proven minimal change disease. CONCLUSIONS: While larger cohorts are needed to ascertain the possibility of a small effect of GLCCI1 SNPs on the steroid-responsiveness of nephrotic syndrome, the GLCCI1 SNPs associated with steroid-responsiveness in asthmatic patients are unlikely to have a clinically actionable impact in pediatric nephrotic syndrome.
BACKGROUND: Empiric steroid therapy is the first-line therapy for pediatric nephrotic syndrome, but treatment response is variable. There are few predictors of steroid-responsiveness, although evidence for genetic factors does exist. Single nucleotide polymorphisms (SNPs) have been recently identified in the promoter region of glucocorticoid-induced transcript 1 gene (GLCCI1) which affect steroid-responsiveness in asthmatic patients. Independently, GLCCI1 was identified as a podocyte protein, the loss of which disrupts the function of the glomerular filtration barrier. We therefore examined whether SNPs associated with the steroid-responsive expression of GLCCI1 might predict steroid-responsiveness in nephrotic syndrome. CASE-DIAGNOSIS/TREATMENT: A cohort of 211 pediatric patients with nephrotic syndrome and 102 controls were genotyped; among the cases, 117 were initial steroid responders, while 94 did not respond to oral steroids. No statistically significant differences were noted among the groups, although there was a trend based on the comparison of the small subgroups of steroid-responsive and non-responsive patients with biopsy-proven minimal change disease. CONCLUSIONS: While larger cohorts are needed to ascertain the possibility of a small effect of GLCCI1 SNPs on the steroid-responsiveness of nephrotic syndrome, the GLCCI1 SNPs associated with steroid-responsiveness in asthmatic patients are unlikely to have a clinically actionable impact in pediatric nephrotic syndrome.
Authors: Giulio Genovese; David J Friedman; Michael D Ross; Laurence Lecordier; Pierrick Uzureau; Barry I Freedman; Donald W Bowden; Carl D Langefeld; Taras K Oleksyk; Andrea L Uscinski Knob; Andrea J Bernhardy; Pamela J Hicks; George W Nelson; Benoit Vanhollebeke; Cheryl A Winkler; Jeffrey B Kopp; Etienne Pays; Martin R Pollak Journal: Science Date: 2010-07-15 Impact factor: 47.728
Authors: Debbie S Gipson; Susan F Massengill; Lynne Yao; Shashi Nagaraj; William E Smoyer; John D Mahan; Delbert Wigfall; Paul Miles; Leslie Powell; Jen-Jar Lin; Howard Trachtman; Larry A Greenbaum Journal: Pediatrics Date: 2009-07-27 Impact factor: 7.124
Authors: Carlos E Araya; Clive H Wasserfall; Todd M Brusko; Wei Mu; Mark S Segal; Richard J Johnson; Eduardo H Garin Journal: Pediatr Nephrol Date: 2006-03-07 Impact factor: 3.714
Authors: Todd D Nebesio; Jamie L Renbarger; Zeina M Nabhan; Sydney E Ross; James E Slaven; Lang Li; Emily C Walvoord; Erica A Eugster Journal: Int J Pediatr Endocrinol Date: 2016-09-26